Pluronic F127 Micelles Improve The Stability and Enhance The Anticancer Stem Cell Efficacy of Citral in Breast Cancer

Abstract

Aim: Improving the stability and anti-cancer stem cell (CSC) activity of citral, a natural ALDH1A inhibitor. Materials & methods: Citral-loaded micelles (CLM) were obtained using Pluronic^® F127 and its efficacy tested on the growth of four breast cancer cell lines. The impact of the CLM on the growth and functional hallmarks of breast CSCs were also evaluated using mammosphere and CSC reporter cell lines. Results: CLM improved the stability and growth inhibitory effects of citral. Importantly, CLM fully blocking the stemness features of CSCs (self-renewal, differentiation and migration) and in combination with paclitaxel CLM sensitized breast cancer cells to the chemotherapy. Conclusion: Targeting CSCs with CLM could improve the treatment of advanced breast cancer in combination with the standard chemotherapy.

Keywords::

• breast cancer
• cancer stem cells
• citral
• F127
• Pluronic^®
• polymeric micelles

Author contributions

MM Abu-Serie designed and performed most of the experiments and wrote the first version of the manuscript and revised it. F Andrade and D Rafael conducted work on the CML synthesis and characterization. P Cámara-Sánchez, J Seras-Franzoso, ZV Díaz-Riascos and P Gener contributed to the in vitro assays, CSC and tdTomato models. S Schwartz Jr. and I Abasolo supervised the work, provided funding, revised data curation and contributed to the writing-editing. All authors approved the final version of the manuscript.

Financial & competing interests disclosure

This work was supported by Science, Technology & Innovation Funding Authority (STDF)-Egypt (short term fellowship, No. 24230 to MM Abu-Serie) and Fondo de Investigaciones Sanitarias (FIS, grants PI20/01474 and PI18/00871, to S Schwartz Jr. and I Abasolo, respectively) of Instituto Carlos III (ISCIII), co-financed by the European Regional Development Fund (ERDF). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Acknowledgments

Some of the equipment used in this work belonged to the ICTS Nanbiosis, more specifically to the U20 or in vivo Experimental Platform of the Functional Validation & Preclinical Research (FVPR) area (http://www.nanbiosis.es/portfolio/u20-in-vivo-experimental-platform/).

Additional information

Funding

This work was supported by Science, Technology & Innovation Funding Authority (STDF)-Egypt (short term fellowship, No. 24230 to MM Abu-Serie) and Fondo de Investigaciones Sanitarias (FIS, grants PI20/01474 and PI18/00871, to S Schwartz Jr. and I Abasolo, respectively) of Instituto Carlos III (ISCIII), co-financed by the European Regional Development Fund (ERDF). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.